Combined Oral Contraceptive Use and the Risk of Cervical Cancer: Literature Review / Uso de anticoncepcional oral combinado e o risco de câncer cervical: Revisão da literatura

Abstract Cervical cancer (CC) is caused by persistent infection of human papillomavirus of high oncogenic risk (hr-HPV); however, several cofactors are important in its carcinogenesis, such as smoking, multiparity, and prolonged use of oral hormonal contraceptives (COCs). Worldwide, 16% of women use COCs, whereas in Brazil this rate is of ~ 30%. The safety and adverse effects of COCs are widely discussed in the literature, including the increase in carcinogenic risk. Due to the existence of several drugs, combinations, and dosages of COCs, it is hard to have uniform information in epidemiological studies. Our objective was to perform a narrative review on the role of COCs use in the carcinogenesis of cervical cancer. Several populational studies have suggested an increase in the incidence of cervical cancer for those who have used COCs for > 5 years, but other available studies reach controversial and contradictory results regarding the action of COCs in the development of CC.

Resumo O câncer cervical (CC) é causado pela infecção persistente pelo papilomavírus humano de alto risco oncogênico (hr-HPV); entretanto, vários cofatores são importantes na sua carcinogênese, como tabagismo, multiparidade e uso prolongado de contraceptivos hormonais orais (COCs). No mundo, 16% das mulheres usam AOCs, enquanto no Brasil essa taxa é de ~ 30%. A segurança e os efeitos adversos dos COCs são amplamente discutidos na literatura, incluindo o aumento do risco carcinogênico. Devido à existência de várias drogas, combinações e dosagens de COCs, é difícil ter informações uniformes em estudos epidemiológicos. Nosso objetivo foi realizar uma revisão narrativa sobre o papel do uso de COCs na carcinogênese do câncer cervical. Vários estudos populacionais têm sugerido aumento da incidência de câncer de colo uterino para aquelas que usam COCs há mais de 5 anos, mas outros estudos disponíveis chegam a resultados controversos e contraditórios quanto à ação dos COCs no desenvolvimento do CCU.

O uso de métodos contraceptivos hormonais em pacientes com asma: repercussões clínicas / The use of hormonal contraceptives methods in patients with asthma: clinical repercussions

Objetivo: Analisar o uso dos contraceptivos hormonais em mulheres com asma e a escolha desses métodos contraceptivos para essa população, com avaliação de eventuais repercussões sobre novos episódios de asma e sibilos. Métodos: Foram selecionados estudos longitudinais, ensaios clínicos, revisões sistemáticas e metanálises. As plataformas consultadas foram PubMed, Embase, Cochrane e SciELO, com a utilização dos descritores: "contracepção", "contracepção hormonal", "sistema intrauterino liberador de levonorgestrel" e "asma". Resultados: Dois grandes estudos demonstraram que o uso de contraceptivos hormonais esteve associado à redução do risco de novos episódios de asma. Uma revisão sistemática concluiu que os resultados para o uso de contraceptivos hormonais para mulheres com asma foram mistos, com aumento ou redução dos seguintes riscos: novo episódio de asma e aumento da frequência das crises e dos sibilos. O uso da contracepção hormonal em pacientes obesas portadoras de asma é controverso. Conclusão: Os resultados para o uso de contraceptivos hormonais em mulheres com asma são inconsistentes, com relatos de aumento ou de redução do risco de novos episódios. O uso do método contraceptivo deve ser discutido individualmente, levando-se em consideração outros fatores de risco associados e o desejo da mulher. A paciente deverá ser orientada se houver piora dos sintomas clínicos de asma na vigência do uso de qualquer método contraceptivo hormonal.

Objective: To analyze the use of hormonal contraceptives in women with asthma and the choice of this contraceptive method for this population, evaluating possible repercussions on new episodes of asthma and wheezing. Methods: Longitudinal studies, clinical trials, systematic reviews and meta-analyses were selected. Platforms consulted: PubMed, Embase, Cochrane, SciELO, using the descriptors: "contraception", "hormonal contraception", "levonorgestrel-releasing intrauterine system" and "asthma". Results: Two large studies demonstrated that the use of hormonal contraceptives was associated with a reduced risk of new episodes of asthma. A systematic review concluded that the results for the use of hormonal contraceptives for women with asthma were mixed, with increased or decrease in the following risks: new asthma episodes, increased frequency and wheezing. The use of hormonal contraception in obese patients with asthma is controversial. Conclusion: The results for the use of hormonal contraceptives in women with asthma are inconsistent, with reports of increased or reduced risk of new episodes. The use of the contraceptive method should be discussed individually, taking into account other associated risk factors and the woman's desire. The patient will be advised if there is a worsening of the clinical symptoms of asthma while using any hormonal contraceptive method.

Association Between Maternal Hormonal Contraception Use and Central Nervous System Tumors in Children.

Importance: The incidence of central nervous system (CNS) tumors in children appears to be increasing, yet few risk factors are established. There is limited information regarding whether maternal hormonal contraception use increases this risk. Objective: To examine the association between maternal hormonal contraception use and CNS tumors in children (<20 years). Design, Setting, and Participants: In this nationwide cohort study based on population-based registry data, 1 185 063 children born in Denmark between January 1, 1996, and December 31, 2014, were followed up for a diagnosis of a CNS tumor (final follow-up on December 31, 2018). Exposures: Maternal hormonal contraception use was analyzed according to any use, regimen (combined/progestin only), and route of administration (oral/nonoral), categorized as recent use (≤3 months before start and during pregnancy), previous use (>3 months before start of pregnancy), and no use. For injections, implants, and intrauterine devices that are used for a different time period, the categorization was appropriately altered. Main Outcomes and Measures: Hazard ratio (HR) and incidence rate difference (IRD) of CNS tumors diagnosed at younger than 20 years. Results: After 15 335 990 person-years of follow-up (mean follow-up, 12.9 years), 725 children were diagnosed with a CNS tumor. The mean age at diagnosis was 7 years, and 342 (47.2%) of the diagnosed children were female. The adjusted incidence rate of CNS tumors per 100 000 person-years was 5.0 for children born to mothers with recent hormonal contraception use (n = 136 022), 4.5 for children born to mothers with previous use (n = 778 843), and 5.3 for children born to mothers with no use (n = 270 198). The corresponding HRs were 0.95 ([95% CI, 0.74-1.23]; 84 children with CNS tumors; IRD, -0.3 [95% CI, -1.6 to 1.0]) for recent use and 0.86 ([95% CI, 0.72-1.02]; 421 children with CNS tumors; IRD, -0.8 [95% CI, -1.7 to 0.0]) for previous use, compared with no use. No statistically significant associations were found for recent or previous use of oral combined, nonoral combined, oral progestin only, or nonoral products compared with no use of hormonal contraception. Conclusions and Relevance: Among Danish children, there was no statistically significant association between any maternal hormonal contraception use and CNS tumor risk.

Association of Hormonal Contraceptive Use With Adverse Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials and Cohort Studies.

Importance: Meta-analyses have reported conflicting data on the safety of hormonal contraception, but the quality of evidence for the associations between hormonal contraceptive use and adverse health outcomes has not been quantified in aggregate. Objective: To grade the evidence from meta-analyses of randomized clinical trials (RCTs) and cohort studies that assessed the associations between hormonal contraceptive use and adverse health outcomes among women. Data Sources: MEDLINE, Embase, and the Cochrane Database of Systematic Reviews were searched from database inception to August 2020. Search terms included hormonal contraception, contraceptive agents, progesterone, desogestrel, norethindrone, megestrol, algestone, norprogesterones, and levonorgestrel combined with terms such as systematic review or meta-analysis. Evidence Review: The methodological quality of each meta-analysis was graded using the Assessment of Multiple Systematic Reviews, version 2, which rated quality as critically low, low, moderate, or high. The Grading of Recommendation, Assessment, Development and Evaluations approach was used to assess the certainty of evidence in meta-analyses of RCTs, with evidence graded as very low, low, moderate, or high. Evidence of associations from meta-analyses of cohort studies was ranked according to established criteria as nonsignificant, weak, suggestive, highly suggestive, or convincing. Results: A total of 2996 records were screened; of those, 310 full-text articles were assessed for eligibility, and 58 articles (13 meta-analyses of RCTs and 45 meta-analyses of cohort studies) were selected for evidence synthesis. Sixty associations were described in meta-analyses of RCTs, and 96 associations were described in meta-analyses of cohort studies. Among meta-analyses of RCTs, 14 of the 60 associations were nominally statistically significant (P ≤ .05); no associations between hormonal contraceptive use and adverse outcomes were supported by high-quality evidence. The association between the use of a levonorgestrel-releasing intrauterine system and reductions in endometrial polyps associated with tamoxifen use (odds ratio [OR], 0.22; 95% CI, 0.13-0.38) was graded as having high-quality evidence, and this evidence ranking was retained in the subgroup analysis. Among meta-analyses of cohort studies, 40 of the 96 associations were nominally statistically significant; however, no associations between hormonal contraceptive use and adverse outcomes were supported by convincing evidence in the primary and subgroup analyses. The risk of venous thromboembolism among those using vs not using oral contraception (OR, 2.42; 95% CI, 1.76-3.32) was initially supported by highly suggestive evidence, but this evidence was downgraded to weak in the sensitivity analysis. Conclusions And Relevance: The results of this umbrella review supported preexisting understandings of the risks and benefits associated with hormonal contraceptive use. Overall, the associations between hormonal contraceptive use and cardiovascular risk, cancer risk, and other major adverse health outcomes were not supported by high-quality evidence.

Adverse events related to oral hormonal contraceptive use in undergraduate pharmacy students: a cross-sectional study

Abstract We aimed to measure the prevalence of adverse events related to oral hormonal contraceptive (OHC) use and their associated factors in undergraduate pharmacy students. A cross-sectional study was conducted by using an online questionnaire for female students of the Faculty of Pharmaceutical Sciences of the University of São Paulo from July to August 2020. A descriptive analysis of the data was carried out, which was followed by determining the prevalence ratios to identify possible factors associated with adverse events resulting from OHC. A total of 269 valid responses were obtained, among which 50.2% (n = 135) of the students reported using OHC as a contraceptive method and 21.2% (n = 57) affirmed that they had at least one adverse event related to OHC use, which corresponds to 42.2% of those who had used OHC. The most common adverse event was headache (70.2%), and a period of less than one month was the most cited (49.1%). Only migraine comorbidity was associated with the occurrence of adverse events related to OHC. These findings reinforce the high incidence of adverse events among OHC users and the low rate of discontinuation due to these events. There is a need to provide more information on contraceptive methods to users, including its risks and contraindications.

Association between the use of hormonal contraceptives and risk of cholecystectomy in women of reproductive age.

PURPOSE: Previous studies have indicated an increased risk of gallbladder disease with hormonal contraceptives although with discordant results. The potential increased risk of gallbladder disease with hormonal contraceptives is concerning given that women are at increased risk of this disease. Thus, the aim of this study was to examine risk of surgery-confirmed gallbladder disease (cholecystectomy) with oral contraceptives, intrauterine devices, and injectable hormonal contraceptives. METHODS: We conducted a retrospective cohort study. Females aged 15-45 who initiated hormonal contraceptive use were identified in the United States IQVIA Ambulatory electronic medical record database between 2008 and 2018. Cox proportional hazards models were used to estimate adjusted hazards ratios and 95% confidence intervals for cholecystectomy with eight formulations of contraceptives compared with levonorgestrel and ethinyl estradiol combined oral contraceptive. Sensitivity analysis was conducted by lagging exposure by 90 days and by excluding patients with history of gallbladder disease. Secondary analyses were conducted by cumulative duration of use. RESULTS: We identified 1,425,821 females who initiated the use of hormonal contraceptives and generated 4417 cholecystectomy events. Overall, the use of medroxyprogesterone acetate (HR: 1.22, 95% CI: 1.07-1.40) and at least 1 year of levonorgestrel intrauterine device use (HR: 1.74: 95% CI: 1.19-2.54) were associated with increased risk of cholecystectomy when compared with levonorgestrel and ethinyl estradiol combined oral contraceptive. However, we did not observe an increased risk with other hormonal contraceptives. Consistent results were observed across sensitivity analyses. CONCLUSION: In this large population-based study, there was an increased risk of cholecystectomy with medroxyprogesterone acetate and intrauterine device but not other hormonal contraceptives. Additional large observational studies are required to corroborate these findings.

Uterine synechiae after intrauterine device use: a case series.

PURPOSE: The intrauterine device (IUD) is one of the most effective and safe contraceptive methods. Substantial literature suggests an overall return to normal fertility following IUD removal. However, there are no studies to date that evaluate endometrial function specifically in nulliparous women after levonorgestrel IUD use. METHODS: We present three nulliparous women with a history of levonorgestrel IUD use who were evaluated for uterine dysfunction at the University of California, San Francisco Center for Reproductive Health. These patients had no other known risk factors or history of uterine manipulation, including prior uterine surgery, pelvic radiation, intrauterine infection, hypothalamic amenorrhea, or uterine anomaly. RESULTS: Upon evaluation, these patients were found to have uterine synechiae concerning for Asherman syndrome. All three patients were eventually able to conceive through assisted reproductive technology or natural conception. CONCLUSION: This case series is the first to suggest a possible effect of endometrial dysfunction on fertility resumption following levonorgestrel IUD removal in nulliparous patients. It is possible that a small subset of patients may be at risk for Asherman syndrome after IUD use. Larger prospective trials are needed to explore this possible association.

Continuation rates of the 52-mg levonorgestrel-releasing intrauterine system according to the primary reason for its use / Taxas de continuação com o sistema intrauterino de liberação de levonorgestrel de 52mg de acordo com o motivo principal de seu uso

Abstract Objective To evaluate whether continuation rates with the 52-mg levonorgestrelreleasing intrauterine system (LNG-IUS) up to 5 years after placement differed between women using the method exclusively for contraception and those using the device for medical reasons alone. Methods A retrospective cohort study was conducted in a family planning clinic with 5,034 LNG-IUS users: 4,287 using the method exclusively for contraception and 747 for medical reasons alone. The continuation rate at 1 to 5 years of use was calculated by life table analysis. Results Initially, the continuation rate was significantly higher in the contraception group: 85.8 versus 83.4 and 77.4 versus 76.0 per 100 women-years in the 1st and 2nd years of use, respectively. There were more discontinuations due to bleeding/spotting in the medical reasons group in the first two years. The discontinuation rate according to reason for use was not significantly different from the third to the fifth year of use. No women discontinued due to amenorrhea in either group. Conclusion The continuation rate was significantly higher in the contraception group in the first two years of use. Amenorrhea was not a reason for discontinuation in either group, suggesting that counselling in this respect was adequate. Nevertheless, counselling could perhaps have been better with regards to the expected long period of bleeding and spotting in the first two years after placement.

Resumo Objetivo Avaliar a taxa de continuação até 5 anos de uso do sistema intrauterino liberador de 52-mg levonorgestrel por dia (SIU LNG) -IUS) é diferente entre mulheres que o usam exclusivamente como anticoncepcional que entre as que usam exclusivamente por razões médicas. Métodos Estudo retrospectivo realizado em uma clínica de Planejamento Familiar 5.034 usuárias de SIU LNG, 4.287 que optaram pelo método apenas como anticoncepcional e 747 que o usavamsomente por razoesmédicas. A taxa de continuação de um até cinco ano foi calculada por meio de análise de tabela de vida Resultados No início a taxa de continuação foi significativamente maior no grupo da anticoncepção: 85,8 versus 83,4 e 77,4 versus 76,0 por 100 anos-mulher no 1° e 2° ano de uso, respectivamente. Houve mais descontinuações por sangrado-manchado no grupo de razões médicas nos dos primeiros anos. A taxa de continuação não foi significativamente diferente desde o terceiro até o quinto ano de uso. Nenhuma mulher de ambos os grupos descontinuou por amenorreia. Conclusão A taxa de continuação foi significativamente maior no grupo de anticoncepção durante os dos primeiros anos de uso. Amenorreia não foi motivo de descontinuação em ambos os grupos, sugerindo que a orientação a esse respeito foi adequada. Entretanto, a orientação referente ao longo período de sangramentos irregulares nos dois primeiros anos após a inserção, precisaria ser melhorado.

Bias Analysis Gone Bad.

Quantitative bias analysis comprises the tools used to estimate the direction, magnitude, and uncertainty from systematic errors affecting epidemiologic research. Despite the availability of methods and tools, and guidance for good practices, few reports of epidemiologic research incorporate quantitative estimates of bias impacts. The lack of familiarity with bias analysis allows for the possibility of misuse, which is likely most often unintentional but could occasionally include intentional efforts to mislead. We identified 3 examples of suboptimal bias analysis, one for each common bias. For each, we describe the original research and its bias analysis, compare the bias analysis with good practices, and describe how the bias analysis and research findings might have been improved. We assert no motive to the suboptimal bias analysis by the original authors. Common shortcomings in the examples were lack of a clear bias model, computed example, and computing code; poor selection of the values assigned to the bias model's parameters; and little effort to understand the range of uncertainty associated with the bias. Until bias analysis becomes more common, community expectations for the presentation, explanation, and interpretation of bias analyses will remain unstable. Attention to good practices should improve quality, avoid errors, and discourage manipulation.

Duration, recency, and type of hormonal contraceptive use and antimüllerian hormone levels.

OBJECTIVE: To assess whether the duration, recency, or type of hormonal contraceptive used is associated with antimüllerian hormone (AMH) levels, given that the existing literature regarding the association between hormonal contraceptive use and AMH levels is inconsistent. DESIGN: Cross-sectional study. SETTING: Baseline data from the Study of the Environment, Lifestyle and Fibroids Study, a 5-year longitudinal study of African American women. PATIENT(S): The patients were 1,643 African American women aged 23-35 years at the time of blood drawing (2010-2012). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Serum AMH level was measured by an ultrasensitive enzyme-linked immunosorbent assay. Linear regression models were used to estimate percent differences in mean AMH levels and 95% confidence intervals (CIs) according to use of hormonal contraceptives, with adjustment for potential confounders. RESULT(S): In multivariable-adjusted analyses, current users of hormonal contraceptives had 25.2% lower mean AMH levels than non-users of hormonal contraceptives (95% CI: -35.3%, -13.6%). There was little difference in AMH levels between former users and non-users of hormonal contraceptives (-4.4%; 95% CI: -16.3%, 9.0%). AMH levels were not appreciably associated with cumulative duration of use among former users or time since last use among non-current users. Current users of combined oral contraceptives (-24.0%; 95% CI: -36.6%, -8.9%), vaginal ring (-64.8%; 95% CI: -75.4%, -49.6%), and depot medroxyprogesterone acetate (-26.7%; 95% CI: -41.0%, -8.9%) had lower mean AMH levels than non-users. CONCLUSION(S): The present data suggest that AMH levels are significantly lower among current users of most forms of hormonal contraceptives, but that the suppressive effect of hormonal contraceptives on AMH levels is reversible.

Depot medroxyprogesterone acetate (DMPA) enhances susceptibility and increases the window of vulnerability to HIV-1 in humanized mice.

The progestin-based hormonal contraceptive Depot Medroxyprogesterone Acetate (DMPA) is widely used in sub-Saharan Africa, where HIV-1 is endemic. Meta-analyses have shown that women using DMPA are 40% more likely than women not using hormonal contraceptives to acquire Human Immunodeficiency Virus (HIV-1). Therefore understanding how DMPA increases susceptibility to HIV-1 is an important public health issue. Using C57BL/6 mice and our previously optimized humanized mouse model (NOD-Rag1tm1Mom Il2rgtm1Wjl transplanted with hCD34-enriched hematopoietic stem cells; Hu-mice) where peripheral blood and tissues are reconstituted by human immune cells, we assessed how DMPA affected mucosal barrier function, HIV-1 susceptibility, viral titres, and target cells compared to mice in the diestrus phase of the estrous cycle, when endogenous progesterone is highest. We found that DMPA enhanced FITC-dextran dye leakage from the vaginal tract into the systemic circulation, enhanced target cells (hCD68+ macrophages, hCD4+ T cells) in the vaginal tract and peripheral blood (hCD45+hCD3+hCD4+hCCR5+ T cells), increased the rate of intravaginal HIV-1 infection, extended the window of vulnerability, and lowered vaginal viral titres following infection. These findings suggest DMPA may enhance susceptibility to HIV-1 in Hu-mice by impairing the vaginal epithelial barrier, increasing vaginal target cells (including macrophages), and extending the period of time during which Hu-mice are susceptible to infection; mechanisms that might also affect HIV-1 susceptibility in women.

An exploratory study on the association of lifestyle factors with serum etonogestrel concentrations among contraceptive implant users.

PURPOSE: To explore how diet and exercise habits associate with serum etonogestrel concentrations among contraceptive implant users. MATERIALS AND METHODS: We conducted a secondary analysis of healthy, reproductive-age women using etonogestrel implants. This study was registered on ClinicalTrials.gov, NCT03092037. We assessed diet and exercise habits with two validated surveys: Healthy Eating Vital Signs and the Stanford Brief Activity Survey. Participants previously had their serum etonogestrel concentrations measured using a validated liquid-chromatography mass-spectrometry assay. We then used linear modelling to test for associations between survey responses and serum etonogestrel concentrations. RESULTS: Among 129 participants, diet and exercise habits had no significant associations with serum etonogestrel concentrations (p = 0.22-0.72), with inconsistent effects found for increased caloric intake and sedentary lifestyle. CONCLUSION: This exploratory study found no significant effect of diet or exercise habits on steady-state pharmacokinetics among contraceptive implant users. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT03092037.

The paradigm of norgestimate: a third-generation testosterone-derivative progestin with a peripheral anti-androgenic activity and the lowest risk of venous thromboembolism.

INTRODUCTION: Norgestimate (NGM) is a testosterone derivative with peculiar receptor activities. AREAS COVERED: This is a narrative review of the available data on the pharmacotherapy of NGM in combined hormonal contraceptives (CHCs) in terms of contraceptive efficacy, venous thromboembolism (VTE) risk, safety, tolerability and bleeding patterns. A comprehensive literature review was conducted in August 2020 using PubMed with the keyword 'norgestimate'. EXPERT OPINION: NGM shows a mild estrogenic activity associated with anti-mineralocorticoid and anti-androgenic properties, largely responsible for the cardiovascular safety profile. The anti-androgenic property depends on the androgen receptor (AR) nuclear translocation (AR trafficking and its subnuclear distribution), the inhibition of 5α-reductase activity (it possesses higher activity compared to other available progestins), and the increase on sexual hormone binding globulin (SHBG) levels if combined with an estrogenic counterpart. NGM is one of the molecules that best modulates the power of ethinyl-estradiol on the thromboembolic risk, being associated with the lowest VTE risk between different CHCs. NGM has the advantage of retaining peripheral anti-androgenic activity, demonstrated by the impact on lipid and glucose metabolism, and it should be preferred if compared with other similar progestins of the same class of risk which are much more androgenic, such as levonorgestrel.

Twelve-month Continuation of the Etonogestrel Implant in Adolescents With Polycystic Ovary Syndrome.

STUDY OBJECTIVE: To identify why adolescents with polycystic ovary syndrome (PCOS) chose the etonogestrel (ENG) contraceptive implant, to determine the 12-month continuation rate, and to characterize factors related to discontinuation. DESIGN, SETTING, AND PARTICIPANTS: Retrospective chart review of adolescents seen at a tertiary care children's hospital between July 1, 2008, and August 30, 2019, with PCOS diagnosis confirmed per National Institutes of Health criteria and ≥12-month ENG follow-up. INTERVENTIONS AND MAIN OUTCOME MEASURES: Demographic characteristics, reasons for ENG insertion and removal, and information on other hormonal/contraceptive therapies were collected. Patients were categorized as ENG continuers (use ≥12 months) or discontinuers (removal at <12 months), and groups were compared. RESULTS: A total of 96 patients met inclusion criteria (age 17.7 ± 2.2 years, body mass index 34.8 ± 8 kg/m2). Reasons for ENG were documented in 74% (51% contraception, 32% ease of use, 15% other, 13% estrogen avoidance). In all, 27% had never been sexually active, and 67% had had prior sexual activity. Treatments prior to ENG placement included 74% combined hormonal contraception, 20% medroxyprogesterone acetate withdrawal, and 17% depot medroxyprogesterone. A total of 77% continued ENG at 12 months. The main reasons for discontinuation were bleeding (41%), concern about weight gain (23%), and mood changes (18%). No preimplantation characteristics were independently predictive of continuation, although 100% of patients with type 2 diabetes (n = 11) continued. Patients who sought additional care, including telephone calls (41% vs 12%, P = .006) and clinic visits (64% vs 20%, P < .001) were more likely to discontinue. CONCLUSIONS: The ENG implant was well tolerated in adolescents with PCOS and similar to published 12-month continuation rates.

Norethisterone and its acetate - what's so special about them?

INTRODUCTION: Progestogens (progestins) are widely used for contraception, in postmenopausal hormone therapy, and in treatment of abnormal uterine bleeding and endometriosis. Norethisterone (NET) and its acetate (NETA) differ from other progestogens by their partial conversion to ethinylestradiol (EE). We review their special characteristics and focus on the clinically relevant risk factors associated with estrogen action, such as migraine with aura and risk of thrombosis. METHODS: Narrative review based on a medical literature (OvidMedline and PubMed) search. RESULTS: NET converts to significant amounts of EE; 10-20 mg NET corresponds to 20-30 µg EE. The effects of NET on the endometrium are pronounced, making it a good choice for treating abnormal uterine bleeding, endometriosis, and endometrial hyperplasia. NET also has beneficial effects on bone mineral density and positive or neutral effects on cardiovascular health. Conversely, long-term use of NET is associated with a slightly increased breast cancer risk, and the risk of venous thromboembolism is moderately increased. This risk seems to be dose-dependent; contraceptive use carries no risk, but therapeutic doses might be associated with an increased risk. Studies suggest an association between combinations of EE and progestogens and ischaemic stroke, which in particular concerns women with migraine. No studies have, however, assessed this risk related to the therapeutic use of NET. CONCLUSIONS: NET is a potent progestogen, especially when considering the endometrium. Its partial conversion to EE, however, is important to remember. Clinical consideration is required with women at high risk for either breast cancer or thromboembolism, or experiencing migraine with aura.

Pharmacokinetic Approach of Clinically Important Drug Interactions of Hormonal Contraceptives - A Review.

Hormonal contraceptives contain an Estrogen and/or a Progestin, which are the substrates of the CYP3A4 enzyme and the drugs inducing the CYP3A4 enzyme can decrease the plasma concentrations and thereby therapeutic efficacy of Hormonal contraceptives resulting in unintended pregnancy. Moreover, the hormonal contraceptives associated risk of thrombotic events are further exacerbated by the simultaneous administration of drugs like Tranexamic acid and tobacco smoke. Therefore, while prescribing hormonal contraception and other drugs to women, drug interactions should always be considered because there could be a possible contraceptive failure or other adverse drug effects. This article provides a summary of guidance to healthcare professionals such as prescribers and pharmacists on pharmacokinetic based interactions between hormonal contraception and other drugs.

Prevalence of Chlamydia trachomatis in an asymptomatic female population attending cervical cytology services of three healthcare centers in Medellín, Colombia / Prevalencia de Chlamydia trachomatis en la población femenina asintomática atendida en los servicios de citología cervical de tres instituciones prestadoras de servicios de salud en Medellín, Colombia.

Introduction: The sexually transmitted infection caused by Chlamydia trachomatis is the most common of bacterial etiology in the world. Although it can be asymptomatic in most cases, it can produce several reproductive health problems in women such as cervicitis, endometritis, and salpingitis. Despite its importance, the epidemiological data on this infection is insufficient in Medellín. Objective: To determine the prevalence of C. trachomatis in women from Medellín, identify possible risk factors, and evaluate its relationship with the human papillomavirus infection (HPV). Materials and methods: We conducted a multicenter cross-sectional study to detect C. trachomatis infection in 1,282 women using PCR and the LightMix 480 HT CT/NG™ commercial kit (Roche, Basel, Switzerland). Results: The total prevalence of C. trachomatis infection was 4.1% (95% CI: 2.9-5.3). We found an association between the presence of the infection and age, cigarette consumption, and the use of hormonalcontraceptives. Conclusion: The prevalence of the infection is similar to that reported in other parts of the world with young women being the most affected population. No relation was found with the presence of HPV.

Introducción. La infección de transmisión sexual causada por Chlamydia trachomatis es la más frecuente de etiología bacteriana en el mundo. Aunque puede ser asintomática en la mayoría de los casos, C. trachomatis puede generar diversos problemas de salud reproductiva en mujeres, como cervicitis, endometritis y salpingitis. A pesar de su importancia, en Medellín no se cuenta con suficientes datos epidemiológicos sobre esta infección. Objetivo. Determinar la prevalencia de C. trachomatis en mujeres de Medellín, determinar los posibles factores de riesgo y evaluar la relación con la infección por el virus de papiloma humano (HPV). Materiales y métodos. Se hizo un estudio transversal multicéntrico para detectar la infección por C. trachomatis en 1.282 mujeres mediante reacción en cadena de la polimerasa (PCR) convencional y el estuche comercial LightMix 480 HT CT/NG™ (Roche, Basilea, Suiza). Resultados. La prevalencia total de la infección por C. trachomatis fue de 4,1 % (IC95% 2,9-5,3). Se encontró una relación significativa de la infección con la edad, el consumo de cigarrillo y el uso de anticonceptivos hormonales. Conclusión. La prevalencia de la infección es similar a la reportada en otros lugares del país y del mundo, siendo las mujeres más jóvenes las más afectadas. En cuanto a la presentación del HPV, no se encontró ningún tipo de relación con C. trachomatis.

What is the best drug treatment for premenopausal women with bleeding irregularities using the levonorgestrel-releasing intrauterine system? A systematic review.

OBJECTIVE: Up to 60% of women discontinue using the levonorgestrel-releasing intrauterine system (LNG-IUS) within 5 years because of bleeding irregularities, pain and/or systemic progestogenic adverse effects. The aim of the study was to assess treatment options for bleeding irregularities in women using the 52 mg LNG-IUS. METHODS: Database searches of Medline, Embase/Ovid and the Cochrane Library were carried out, and journals were searched by hand, for relevant studies published from database inception to March 2020. Inclusion criteria were randomised controlled trials (RCTs), prospective cohort studies and case-control studies of premenopausal women using the LNG-IUS and receiving medical treatment for bleeding irregularities. Screening, data extraction and quality assessment of retrieved articles were carried out independently by two pairs of reviewers. The primary outcome was the reduction of bleeding/spotting days. RESULTS: Of the 3061 studies identified, eight met our inclusion criteria: six RCTs and two prospective cohort studies. The eight studies enrolled a total of 677 women who were treated with tamoxifen, mifepristone, ulipristal acetate, naproxen, oestradiol, mefenamic acid, tranexamic acid or the progesterone receptor modulator CDB 2914. The results of our analysis indicated that naproxen may be effective for the prophylactic treatment of bleeding immediately (<12 weeks) after LNG-IUS insertion (high level of evidence). Oestradiol may be effective in treating ongoing bleeding irregularities >6 months after insertion (low level of evidence). CONCLUSION: Evidence for the medical treatment of (ongoing) bleeding irregularities during use of the LNG-IUS is lacking and more research is needed on the topic.

Long-term efficacy and feasibility of levonorgestrel-releasing intrauterine device use in patients with adenomyosis.

To evaluate the efficacy and feasibility of levonorgestrel-releasing intrauterine device (LNG-IUD) use longer than 5 years in women with adenomyosis.Data were retrospectively collected from patients who were treated with LNG-IUD longer than 5 years at the Chungnam National University hospital for adenomyosis diagnosed with ultrasonography from January 2006 to November 2013.A total of 131 patients who were diagnosed with adenomyosis had treated with LNG-IUD longer than 5 years. The mean duration of keeping 1 device without replacement was 58.35 ±â€Š15.98 months, and total duration of LNG-IUD treatment was 83.86 ±â€Š23.88 months. A total of 51 patients stopped using LNG-IUD after 5 years and the mean age at the time of LNG-IUD removal was 52.46 ±â€Š6.9. LNG-IUD treatment had a significant effect on both menorrhagia and dysmenorrhea starting from the first month of insertion (P < .01), which persisted until 6 years when the effect started to plateau. The decrease in uterine volume was not consistent during the treatment period. The uterine volume decreased significantly only in the first and second year of LNG-IUD treatment and then from eighth to tenth year of LNG-IUD treatment (P < .05). Adverse events after insertion of LNG-IUD decreased significantly after 5 years.LNG-IUD treatment longer than 5 years is an effective and feasible method for patients diagnosed with adenomyosis.